In study after study, the psychoactive drug ketamine has given profound and fast relief to many people suffering from severe depression. But these studies have a critical shortcoming: Participants usually can tell whether they have been given ketamine or a placebo. Even in blinded trials in which participants are not told which they received, ketamine’s oftentimes trippy effects are a dead giveaway.
In a new study, Stanford Medicine researchers devised a clever workaround to hide the psychedelic — or dissociative — properties of the anesthetic first developed in 1962. They recruited 40 participants with moderate to severe depression who were also scheduled for routine surgery, then administered a dose of ketamine or placebo when the participants were in surgery and under general anesthesia.
All researchers and clinicians involved in the trial also were blinded to which treatment patients received. The treatments were revealed two weeks later.
The researchers were amazed to find that both groups experienced the large improvement in depression symptoms usually seen with ketamine.
“I was very surprised to see this result, especially having talked to some of those patients who said ‘My life is changed, I’ve never felt this way before,’ but they were in the placebo group,” said Boris Heifets, MD, PhD, assistant professor of anesthesiology, perioperative and pain medicine, and senior author of the study published Oct. 19 in Nature Mental Health.
Just one day after treatment, both the ketamine and placebo groups’ scores on the Montgomery-Åsberg depression rating scale — a standard measure of depression severity often referred to as the MADRS — dropped, on average, by half. Their scores stayed roughly the same throughout the two-week follow-up.
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